The purpose of this work is to clarify the mechanism of cell transformation by examning the genetic and physiological factors which affect cell transformation induced by chemicals and irradiation. Characterization of cell variants of Balb/3T3 line showing different susceptibility to the chemically or ultraviolet (UV) induced transformation, which have been isolated in our laboratory indicate that variants are different in the expression process by which promoting agents act. These results provide the first genetic evidence for the important role of a promoter-responsive step in the induction of cellular transformation. These variants will be very useful for studying the mechanism of the promotion process. On the other hand, a naturally occurring promoter, dihydroteleocidin B (DHTB), was found to be 100-fold stronger in its ability to enhance the carcinogen-induced transformation than TPA. The extraordinary enhancement of transformation by DHTB is ascribed to its resistance to metabolic inactivation which results in continuous exposure of the cells to active promoter. This suggests that many biochemical changes induced by a single application of promoter may not be directly involved in the promoting process.